Choline is an essential nutrient for human and is involved in many metabolic pathways, including methyl-group transfer. Animal studies have demonstrated choline deficiency as a condition sufficient for the development of hepatocellular carcinoma in the absence of other carcinogens. A methyl-group-deficient diet with no choline and low methionine promotes chemically induced carcinogenesis in animals. A methyl-group-deficient diet with low folate and methionine intake has been related to cancers of several organs in humans. However, understanding the role of choline in humans has been hampered by lack of food composition data for dietary choline intake. Recently, we obtained choline composition data for foods measured by our food frequency questionnaire. Before we use the intake data in populations, we propose to examine the biological relevance of variation in choline intake over the range of intake in a general population. Using data from the Framingham Offspring Study, we will examine the relation between choline intake and plasma levels of homocysteine, an intermediate product in methyl-group metabolism and an indicator of the body's methyl-group availability. We will characterize the relationship between choline intake and other dietary and life-style factors. We will also examine choline intake in relation to colorectal adenoma risk in the Nurses' Health Study, a large prospective study of women. These data will provide evidence whether measurable and physiologically important variation in choline intake exists within populations. The results from the proposed grant will enhance understanding of the role of choline intake in humans and lay the groundwork for future studies on choline intake and overall methyl-group-deficient diet and cancer.